Numerous studies have demonstrated marked changes in the low molecular weight crystallins in human cataracts. We have identified three populations of these proteins, differing in molecular weight, but clearly related to each other immunochemically. The largest of the three species (MW = 24,000) is the component which rapidly disappears from the soluble protein fraction in cataractous tissue. We have identified this fraction, which is clearly related to Gamma-crystallin, as the material which previously has been called Bs-crystallin. It appears that this protein may play a key role in the process of opacification. Oxidation accounts for many of the structural modifications seen in lens proteins during aging and cataractogenesis. We have been studying the effects of various oxidants on rat lenses in organ culture. Singlet oxygen and H202 are strongly toxic to lenses when present in the medium while the direct effects of the superoxide and hydroxyl radicals are minimal. We are now extending these studies to monkey lenses which are more similar to the human lens. A major advantage is the presence in these lenses of the yellow pigment found in human lenses which we have shown previously to be an effective photodynamic sensitizer. Dr. Fred Bettelheim has initiated studies aimed at elucidating the nature of the supermolecular organization of the lens crystallins. By probing homo- and hetero-aggregates of the various crystallins for the presence of hydrophobic sites, charged sites, etc. one can deduce the types of interaction responsible for aggregation of the various crystallin mixtures. Results to date from ammonia sorption experiments indicate that specific types of interactions occur among the various crystallins and that the nature of the interactions varies depending upon the protein composition of the mixture.